The current "epidemic" of obesity is an increasing problem in societies world wide. The search for a long term treatment is an ongoing process with much focus to date on homeostatic factors, particularly in the hypothalamus. The proposed research is designed to address a possible interaction between the striatal acetylcholine system and opioid system with regard to food intake. Our preliminary results indicate that intrastriatal infusions of the muscarinic antagonist scopolamine produce a long-term reduction on food intake and a desensitization of opioid-induced feeding responses. In the current proposal, we will explore various behavioral and neuropharmacological parameters affected by scopolamine treatment. A time course study will be conducted to determine the duration of scopolamine anorexia and further experiments will examine scopolamine-induced alterations in different motivational states and modulation of other striatal neurotransmitter systems. In addition to these experiments, a pharmacokinetic study of scopolamine clearance from striatum will be performed along with neuropharmacological assays to assess the function of the opioid receptor inside the striatum. Relevance to public health: The work outlined in this proposal has the potential to identify a novel neuropharmacological pathway in the control of feeding. This could lead to new drugs for appetitive control, which could help alleviate the obesity epidemic. [unreadable] [unreadable] [unreadable]